TOKYO & LONDON—In January, Heptares Therapeutics published work showing the first high-resolution X-ray crystal structure of the complement C5a receptor binding a small-molecule allosteric antagonist. These results have detailed the location of a new allosteric binding site for the GPCR outside of the transmembrane helical bundle. The C5a receptor features in the innate immune response and is part of the complement system, which partly comprises the body’s response to infection and injury. Complement system inhibitors are of interest as potential treatments for diseases such as rheumatoid arthritis, Crohn’s disease, sepsis and ischemia-reperfusion injuries.

Fiona Marshall, chief scientific officer of Heptares and Sosei, said: “Our ability to determine the structures of GPCRs with high definition alongside our other structure-based drug design technologies and expertise provides a unique opportunity to tackle high value but difficult targets. With the C5a receptor, these capabilities and the insights they generate provide opportunities to design novel and selective therapeutics to address areas of clear medical need.”